Biocatalytic approaches for the synthesis of bioactive molecules

拟议的研究计划调查创新的生物催化方法，以开发功能成分和营养食品。在短期内，该计划的主要重点是开发新的酶促糖基化策略，以有效合成非可消化低聚糖，其在支持肠道健康和降低癌症风险方面的好处正日益得到承认。新型低聚果糖(FOSS)以不同的戊糖或多元醇取代葡萄糖基，已被确定为潜在的候选者。可以想象，这些新的FOSS可能具有新的免疫调节能力和对病原体的抗黏附活性，这是当前一代FOS所没有的。尽管左旋蔗糖酶(LSS)具有催化合成新型FOSS的潜力，但它们的可用性和操作稳定性仍然受到限制。最初的努力集中在从嗜热微生物来源中诱导和回收新的LSS。为了为更好地调节LSS的作用提供合理的基础，拟议研究的一个重要部分将集中在这些酶发挥作用的机制的研究上。控制LS催化的果糖转移的热力学平衡的驱动力也将被研究，以便更好地合成定义明确的FOSS。为了能够方便地调节转移果糖基化过程，将研究LSS在纳米材料载体上的固定化，强调纳米材料的特性与LSS效率之间的关系。进一步探索固定化和分子印迹的合理结合，以提高LS的选择性。生产的自由/开源软件将根据它们的结构和生物活性进行表征。这一具有挑战性的研究计划具有重要的科学意义，因为它将促进新兴的酶糖基化领域的知识，并为在工业水平上开发生物催化过程提供科学基础，以合成潜在的功能性成分的新型FOSS。

The proposed research program investigates innovative biocatalytic approaches toward the development of functional ingredients and nutraceuticals. In the short term, the primary focus of this program is on the development of novel enzymatic glycosylation strategies for efficient synthesis of non-digestible oligosaccharides whose benefits, in supporting intestinal health and reducing the risk of cancers, are being increasingly recognized. Novel fructooligosaccharides (FOSs), headed with different pentoses or polyols instead of a glucosyl moiety, have been identified as potential candidates. These new FOSs may conceivably possess new immunomodulatory capacity and antiadhesive activity against pathogens that are not present in the current FOS generation. Although levansucrases (LSs) are being increasingly recognized for their potential to catalyze the synthesis of novel FOSs, their availability and their operational stability are still limited. Initial efforts have been focused on the induction and the recovery of novel LSs from thermophilic microbial sources. To provide a rational basis for a better modulation of the actions of LSs, an important part of the proposed research will focus on the investigation of the mechanism by which these enzymes function. The driving forces that control the thermodynamic equilibrium of LS-catalyzed transfructosylation will also be studied for a greater-yield synthesis of well-defined FOSs. With the aim of enabling easy modulation of the transfructosylation processes, the immobilization of LSs on nanomaterial supports will be studied, emphasizing the relationships between the features of nanomaterials and the efficiency of LSs. The rational combination of immobilization and molecular imprinting will be further explored to improve the LS selectivity. The produced FOSs will be characterized in terms of their structures and their biological activities. This challenging research program is of scientific importance as it will advance the knowledge in the emerging field of enzymatic glycosylation and provide a scientific-based ground for the development of biocatalytic processes at the industrial level for the synthesis of novel FOSs of a potential use as functional ingredients.